ASHM Report Back

Clinical posts from members and guests of the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine (ASHM) from various international medical and scientific conferences on HIV, AIDS, viral hepatitis, and sexual health.

One of the highlights of the first day of the Glasgow 2016 HIV Drug Congress was a brilliant presentation by Dr Andrew Hill of St Stephen’s AIDS Trust in London on the cost of novel direct-acting antivirals (DAAs) for chronic hepatitis C (HCV).His group extracted data from an online database of Indian export ledgers for per-kilogram prices and volumes of DAA active pharmaceutical ingredients (APIs) exported from India over Jan-Jun 2016.Generic DAAs are being produced by manufacturers in India and a limited number of other countries under voluntary licences offered by Gilead, the originator company of Sofosbuvir; however, these countries only represent 50% of the worldwide epidemic and current high prices elsewhere limit access to DAAs both globally and in high-income countries.

Dr Hill and his research team combined the cost of per-pill API requirements with estimated costs for formulation and excipients and packaging, and finally a profit margin of 50% was added to estimate a price at which generic producers could profitably enter the market.

Their graphs of cost per kilogram of DAAs showed that production costs for these medications have been falling rapidly since 2015.The difference between generic production costs and the current price paid for non-generic DAAs in developed countries is enormous.For example, 12 week treatments of sofosbuvir can currently be manufactured for $62, sofosbuvir+ledipasvir $96, daclatasvir $14, sofosbuvir+velpatasvir $181-216.These prices include the estimated 50% profit margin for generic suppliers.In contrast, the cost of a 12 week course of sofosbuvir available via the non-generic manufacturer in the US is $49,860 – 84,000; of daclatasvir is over $50,000; of sofosbuvir+ledipasvir is $56,700 – 94,500; and of sofosbuvir+velpatasvir is $74,760.

Dr Hill made the point that the estimated generic prices for DAAs are comparable to those that allowed massive treatment scale-up in HIV/AIDs.He also commented that governments are often unaware of the degree of mark-up being charged on medications they are purchasing, although this information is in fact available via the methods his study team used.He stated that the common reaction to talk of these huge profit margins was that pharmaceutical companies need the money to invest in further research and development: his response was to state that Gilead, for example, posted a profit of over 10 billion dollars in the past year, and to pose the question: exactly how much money do such companies need to make to fund further research and development?

Of the plenary session today what really stood out was Anton Pozniaks session ‘TB and Co-infections: the long game. During the session he reminded us that TB is now the leading cause of death for people living with HIV. He detailed steps to disease elimination for TB, hepatitis B and C – a very long game indeed.

In ‘The Living with HIV: Long-Term Effects’ Amanda Mocroft (PDB0101) examined renal function in patients in the START study. eGFR was significantly lower in the deferred arm versus the immediate treatment arm. This finding reached significance in the non-adjusted analysis despite the use of potentially nephrotoxic drugs such as tenofovir. Yet another reason to start ART early.

PrEP has been a major theme at this conference. More good news was provided by Jean-Michel Molinain the extension arm of the Ipergay study (WEAC0102). This study used intermittent PrEP and previously reported the high efficacy of PrEP with TDF/FTC taken ‘on demand’ in high risk MSM – an 86% relative reduction in HIV-incidence in the TDF/FTC arm vs Placebo (95% CI: 40-98, P=0.002). All participants were offered open-label TDF/FTC. During 515 person-years only 1 HIV infection occurred giving a risk of HIV of 0.19 (0.01-1.08) per 100 per year. This patient reported that he had ceased PrEP.

As this combination will be widely used in Australia the next session was very relevant. AnnieLuetkemeyer (WEAB0302) presented ‘Drug-drug interactions studies between HCV antivirals sofosbuvir/velpatasvir and HIV antiretrovirals’. This was a Phase 1 study conducted in healthy volunteers to evaluate potential drug-drug interactions (DDIs) between SOF/VEL and HIV antiretroviral (ARV).

-Increased TFV exposure (~40%) was observed with SOF/VEL when administered as TDF

-Decreased velpatasvir (53%) when given with efavirenz

The author concluded that all study combinations could be used except efavirenz-containing ART. This is an important finding given the number of patients taking Atripla.

And for the rare patients who does not achieve SVR with DAA therapy with sofosbuvir/ledipasvir (Harvoni)? Well they can be retreated with…. Harvoni for 6 months combined with ribavirin. Annie Luetkemeyer (WEPEB060) presented data on 9 HIV/HCV who had not cleared with 12 weeks of Harvoni who were then retreated with 8/9 achieving a SVR.

There’s a particular gentleman at the AIDS 2016 Conference who causes a kerfuffle wherever he goes and I’ve witnessed his performance a number of times over the past few days.

At the end of every session he asks the lecturer “So, what are you doing about TB?”

It’s an AIDS Conference so most speakers are caught off guard when they don’t get a question about AIDS, but on Tuesday a speaker retorted “Well Anton, I didn’t know you were in the room, otherwise I wouldn’t have asked if there were any questions”.

I’m sure you’ll be pleased to hear that Dr Anton Pozniak finally got his own platform to speak in the plenary session.

He informed his captive audience that it’s all very good to treat HIV, but every year in Africa, Tuberculosis causes more deaths. He reminded us that our current TB vaccination is 95 years old and we need a new one.

Tuberculosis is diagnosed too late, with half the diagnoses made at post-mortem. HIV testing is improving, but we also need to be using a rapid test for TB. Whether it’s spitting in a pot or peeing in a jar, we already have the technology to test for Tuberculosis - but we need it to be quick, portable and affordable.

We know Tuberculosis causes significant morbidity and mortality for people living with HIV (PLHIV). We also know that using Anti-Retroviral Therapy (ART) by itself is not sufficient to treat Tuberculosis. ALL patients co-infected with HIV & Tuberculosis need to be treated by a combination of ART and anti-TB medications.

We cannot shorten the duration of Tuberculosis treatment to any less than 6 months using our current anti-TB medications. New drugs are being trialled and some appear promising, but we’re even trialling old drugs to see if they might possibly work for Tuberculosis too.

Nelson Mandela once said “We can’t fight AIDS unless we do much more to fight TB”, but Anton isn’t keen to stop there. He not only wants to fight HIV and Tuberculosis, but he’s keen to eradicate viral hepatitis too.

Anton's dream is for everyone with viral hepatitis to be treated, but this dream comes with a price.

Hepatitis B treatment costs ~$15,000 in the USA, but the estimated true cost is $36. Hepatitis C treatment in the USA costs ~$84,000, but the estimated true cost is $62. Affordable medication can truly change the lives of millions of people around the world, but that's not yet happening.

Anton urged everyone to communicate and combine efforts to provide integrated health services for people in need. Testing and treatment should not only be for HIV, but also for Tuberculosis, Hepatitis B & Hepatitis C.

We’re aiming to end HIV by 2030, but let’s aim to eliminate Hepatitis C and Tuberculosis too.

Anton closed his speech by saying that we need new 90:90:90 goals. We should aim for the cost of HIV treatment to be $90 per year, Hepatitis B treatment should be $90, and Hepatitis C cures should be $90 too.

NB - There was no kerfuffle at the end of his presentation as Dr Anton Pozniak wisely did not ask the audience if they had any questions.

I found the case-based workshop on HCV quite useful. The session highlighted some of the difficult therapeutic scenarios with current DAAs. It also mentioned some of the limitations of current DAAs and research gaps in this area.

Here I have summarised important points relevant to HIV & HCV prescribers. Standard abbreviations are used.

HIV and HCV co-infection

Even though efficacy of current DAAs in HIV/HCV high and generally equivalent to HCV mono-infections, this is still a "special" population with therapeutic challenges

However, the clinical significance of elevated TDF level here is not very clear at this stage. But when LDV/SOF and TDF given, frequent monitoring recommended eg week 2 & 4 renal functions monitoring

What about TAF and LDV/SOF? Data was presented for E/C/F/TAF and R/F/TAF. Tenofovir concentration are increased but well below the concentrations with TDF.

Take home message: LDV/SOF and TDF: Be aware contra-indications and frequent renal function monitoring while on DAAs

DDI with other meds

One important DDI highlighted in the case was PPIs and SOF/LDV. Chronic PPI therapy is not uncommon in PLHIV and in many cases, it is unnecessary. There is significant decrease of LDV concentrations with PPIs. The data from HCV TARGET study sub-analysis was presented. SVR 12 with SOF/LDV was reduced from 90% to 70% when PPIs are used as baseline.

Take home message: PPIs can significantly compromised SOF/LDV efficacy. This is good opportunity to review patients on long term PPIs and cease if not absolutely necessary. One more reason to stop unnecessary long term PPIs

Can we stop HIV treatment temporarily when there are significant DDIs with HIV ART and HCV DAAs? Panel members felt with the available of new HIV ARTs, stopping HIV treatment temporarily is not acceptable and it’s recommenced to change HIV ART to a suitable regimen prior to HCV DAA treatment.

Shorter course of DAAs

In some subpopulations, SOF/LDV and SOF/DCV 8 weeks has high efficacy comparable to 12 weeks treatment.

For an example, In GT1, treatment naive, non-cirrhotic and baseline HCV VL less than 6 million IU/mL treatment can be shorted to 8 weeks of SOF/LDV.

However, data is currently not available for HIV/HCV co-infections. The panel members recommendation was until we have more data for co-infections, avoid 8 weeks treatment.

Take home message: Avoid shorter course (less than 12 week ) of SOF/LDV or SOF/DV in HIV/HCV co-infections until more clinical data available.

As we are aware there are people living with HIV who are also co-infected with Hepatitis C. In Australia approximately 1 in 8 people living with HIV are also co-infected with HCV.

Clara discussed how there is a disparity between those that are mono- infected and those that are co-infected and the number of those that have initiated early administration of ARV's for HIV. The rates of co-infected initiating or are on ARV's are much lower, despite the change in recommendations of early initiation of ARV's for HIV.

There are significant unmet needs for those that are co-infected with HCV. Often this minority population may have chaotic lives, not engage in health services, have financial difficulties, and may have difficulty with medication compliance. Clara discussed issues surrounding the need for wider Alcohol and Other Drugs services, Primary Care services, Allied Health services, as well as the ongoing issues surrounding stigma.

It is hoped that we can help this minority of a minority group improve their health outcomes and quality of life.